AMINOGUANIDINE AMELIORATES SPLANCHNIC HYPOSENSITIVITY TO GLYPRESSIN IN A HEMORRHAGE-TRANSFUSED RAT MODEL OF PORTAL-HYPERTENSION

1. Hyposensitivity to vasopressin is a well-documented phenomenon in a nimals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors o bserved in experimental portal hypertension or in rats with haemorrhag ic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressi n (a long-acting vasopressin analogue) could enhance its portal hypote nsive effect in portal-hypertensive rats with bleeding. 2. Portal hype rtension was induced by partial portal vein ligation. Fourteen days af ter operation, systemic and portal haemodynamics were measured in stab le or bleeding portal vein-ligated rats receiving intravenous glypress in (0.07 mg/kg) or aminoguanidine (70 mg/kg) followed by glypressin in fusion. In rats with a hypotensive haemorrhage, 4.5 ml of blood was wi thdrawn and 50% of the withdrawn blood was reinfused before the admini stration of glypressin or aminoguanidine. 3. Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligat ed ran without bleeding than in those with bleeding (P < 0.001). In co ntrast, glypressin induced similar changes in mean arterial pressure b etween the two groups (P > 0.05). The addition of aminoguanidine signi ficantly potentiated the portal-hypotensive effect of glypressin in bl eeding portal vein-ligated rats (P < 0.005) without an effect on the c hanges in mean arterial pressure induced by glypressin infusion (P > 0 .05). 4. Splanchnic hyposensitivity to glypressin exists in a haemorrh age-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.